We found that the nitrosoureas 1-nitroso-5,6-dihydrouracil (NDHU) and 2-hydroxyethylnitrosourea (HENU), administered chronically per os to rats, were strong carcinogens for the liver, and that HENU was also a strong carcinogen for the duodenum. Our main objective is to explain the biochemical and biological mechanisms by which these two compounds act in the liver and duodenum. Accordingly, we shall investigate whether NDHU and HENU alkylate liver nucleic acids (especially DNA) at different sites from other nitrosoureas which are not liver carcinogens, or cause alkylation that persists longer; cause breaks in the liver DNA molecule as observed by sucrose gradient sedimentation; have specific inhibitory and/or enhancing effects on liver DNA synthesis; are concentrated in the liver or metabolized there to proximate carcinogens; and induce hyperplastic liver nodules when combined with certain other treatments. We shall also explore similar parameters which may explain why HENU acts in the duodenum. As negative controls, parallel studies will be undertaken with ethylnitrosourea and l-nitrosohydantoin.